Type 1 diabetes mellitus is frequently associated with vascular complications accounting for most of the mortality and morbidity of diabetic patients. Macrovascular diseases including coronary heart disease, cerebrovascular disease and peripheral vascular disease occur at an earlier age in the diabetic population. The purpose of this study is to further elucidate the altered Ca 2+ signaling in vascular smooth muscle cells associated with diabetes by defining the upstream regulators that change the expression of intracellular Ca 2+ pumps and ion channels in response to diabetes. Most important the project will determine whether the medical intervention of islet transplantation will reverse the effects of diabetes on smooth muscle Ca 2+ signaling. These aims will be tested using autoimmune diabetic rats that will receive islet transplants after 1, 2, or 6 months of diabetes. At the completion of the studies the femoral artery and aorta will be isolated and dispersed into single smooth muscle cells for confocal microscopy live-cell studies. Tissue homogenates will be used to obtain RNA for Northern hybridization and microarray analysis with RT-PCR. The possibility of reversing the vascular disease associated with diabetes will provide us with tools to elucidate the molecular and cellular mechanisms responsible for diabetes-associated macrovascular disease.